title: Nanoparticles targeting dendritic cell surface molecules effectively block T cell conjugation and shift response.
abstract: Dendritic cells (DCs) are potent professional antigen presenting cells (APC) that activate naïve T cells. Interaction of ICAM-1 and LFA-1 molecules on each cell is required for T cell conjugation to DCs, which leads to naïve CD4+ T cell activation and proliferation. Nanoparticles capable of blocking LFA-1/ICAM-1 interaction were studied as inhibitors of T cell conjugation to DCs. Primary DCs were primed with ovalbumin, then treated with a peptide that binds ICAM-1 (LABL), a peptide that binds LFA-1 (cIBR), or the same peptides covalently linked to the surface of poly(dl-lactic-co-glycolic acid) nanoparticles (NPs). LABL-NPs and cIBR-NPs rapidly bound to DCs and inhibited T cell conjugation to DCs to a greater extent than the free peptides, unconjugated nanoparticles (NPs), anti-ICAM-1 antibodies, and anti-LFA-1 antibodies. In addition, DCs treated with NPs or with cIBR-NPs stimulated the proliferation of T cells, but DCs treated with LABL-NPs did not stimulate T cell proliferation. Nanoparticles targeting ICAM-1 or LFA-1 also altered cytokine production by DC cocultured with T cells when compared to free ligands, suggesting that these NPs may offer a unique tool for shaping T cell response.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kansas, Lawrence, Kansas 66047, United States.
authors.forename: Chuda
authors.initials: C
authors.lastname: Chittasupho
authors.forename: Laura
authors.initials: L
authors.lastname: Shannon
authors.forename: Teruna J
authors.initials: TJ
authors.lastname: Siahaan
authors.forename: Charlotte M
authors.initials: CM
authors.lastname: Vines
authors.forename: Cory
authors.initials: C
authors.lastname: Berkland
mesh_terms: D002478:Cells, Cultured; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D016503:Drug Delivery Systems / Q000379:methods; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D049329:Nanostructures / Q000008:administration & dosage*; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology
chemical_list: D008565:Membrane Proteins